Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms
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- Jan Korbecki
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72 Av., 70-111 Szczecin, Poland
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- Donata Simińska
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72 Av., 70-111 Szczecin, Poland
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- Magdalena Gąssowska-Dobrowolska
- Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland
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- Joanna Listos
- Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland
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- Izabela Gutowska
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72 Av., 70-111 Szczecin, Poland
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- Dariusz Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72 Av., 70-111 Szczecin, Poland
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- Irena Baranowska-Bosiacka
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72 Av., 70-111 Szczecin, Poland
説明
<jats:p>Chronic (continuous, non-interrupted) hypoxia and cycling (intermittent, transient) hypoxia are two types of hypoxia occurring in malignant tumors. They are both associated with the activation of hypoxia-inducible factor-1 (HIF-1) and nuclear factor κB (NF-κB), which induce changes in gene expression. This paper discusses in detail the mechanisms of activation of these two transcription factors in chronic and cycling hypoxia and the crosstalk between both signaling pathways. In particular, it focuses on the importance of reactive oxygen species (ROS), reactive nitrogen species (RNS) together with nitric oxide synthase, acetylation of HIF-1, and the action of MAPK cascades. The paper also discusses the importance of hypoxia in the formation of chronic low-grade inflammation in cancerous tumors. Finally, we discuss the effects of cycling hypoxia on the tumor microenvironment, in particular on the expression of VEGF-A, CCL2/MCP-1, CXCL1/GRO-α, CXCL8/IL-8, and COX-2 together with PGE2. These factors induce angiogenesis and recruit various cells into the tumor niche, including neutrophils and monocytes which, in the tumor, are transformed into tumor-associated neutrophils (TAN) and tumor-associated macrophages (TAM) that participate in tumorigenesis.</jats:p>
収録刊行物
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- International Journal of Molecular Sciences
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International Journal of Molecular Sciences 22 (19), 10701-, 2021-10-02
MDPI AG